This project extends ongoing studies to develop specific molecules capable of inhibiting the enzymes of cariogenic Streptococcus mutans that are involved in the utilization of dietary oligosaccharides. Earlier studies have shown that periodate-oxidized dextran is a potent inhibitor of soluble glucosyltransferases, but does not inhibit cell-bound enzymes, and has no effect on cell-adherence and plaque-forming properties of S. mutans. Emphasis has turned to the development of enzyme inhibitors of lower molecular weight that are able to penetrate dental plaque and decrease the synthesis of insoluble alpha-glucan and the production of acid by the microorganisms. To this end the action patterns of extracellular glucosyltransferases that metabolize sucrose, and the intracellular enzyme system that metabolizes maltodextrins, are being studied in detail. A large number of oligosaccharide substrates and modified substrate analogues are being tested for their effects on these enzyme activities and on the products of their reactions.